This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity is one of the major health challenges facing the developed world, significantly increasing the risk of coronary disease, and of diabetes. It has recently been shown that for every "point" by which a person's body mass index (BMI) exceeds 25, there is an associated increase in the risk of cardiac disease. An estimated 9.4% of US healthcare expenditure is directly related to "obesity and inactivity", while recent costs due to diabetes were estimated at $98 billion per annum. There has become intense interest by pharmaceutical companies to develop a therapeutic intervention that will inhibit food intake and cause controlled and safe weight loss. The melanocortin neurons in the brain produce a neuropeptide that potently inhibits food intake, stimulates energy expenditure and regulates peripheral glucose homeostasis. The importance of the melanocortin system is clearly evident in rodents to humans, whereby mutations or genetic deletion of melanocortin genes cause early onset morbid obesity. In fact mutations of the melanocortin system are the most common monogenic cause of obesity in humans. The overall aim of this study is to determine if treatment with a melanocortin agonist can improve body adiposity and glucose homeostasis in a rhesus macaque model of diet induced obesity. The specific goals of this study are to 1) identify an effective dose of melanocortin agonist for the inhibition of food intake, and 2) determine if long-term treatment with a melanocortin agonist can reduce food intake, body adiposity, and improve insulin sensitivity.